Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Eeza, M. N. H., Singer, R., Ding, Y. et al. 2023. Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging. PLOS ONE 18(4), e0284215.

Leptin is a hormone that plays a key role in controlling food intake and energy homeostasis. Skeletal muscle is an important target for leptin and recent studies have shown that leptin deficiency may lead to...

Malik, A., Zavadil, J. A., Geusz, M. E. 2023. Using bioluminescence to image gene expression and spontaneous behavior in freely moving mice. PLOS ONE 18(1), e0279875.

Bioluminescence imaging (BLI) of gene expression in live animals is a powerful method for monitoring development, tumor growth, infections, healing, and other progressive, long-term biological processes. BLI remains an effective approach for reducing the number...

Palumbo, G., Kunze, L. H., Oos, R. et al. 2023. Longitudinal studies on Alzheimer disease mouse models with multiple tracer PET/CT: Application of reduction and refinement principles in daily practice to safeguard animal welfare during progressive aging. Animals 13(11), 1812.

Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development of new drugs and in the attempt...

Peruga, M., Kawala, B., Sarul, M. et al. 2023. Are currently selected laboratory animals useful in the research of how female hormones influence orthodontic biomechanics? Animals 13(4), 629.

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and...

Cameron, A. S., Rub, A. M. W., Sandford, B. P. 2023. Evaluation of healing progression at surgical incision sites and the use of antiseptics for enhancing post-operative survival in subyearling Chinook salmon (Oncorhynchus tshawytscha). PLOS ONE 18(7), e0288056.

In an attempt to develop more effective surgical implantation methods for fish, surgical incisions typical of those made for implanting micro-acoustic transmitters into the peritoneal cavity were evaluated on a weekly basis for healing progression...

Klabukov, I., Shestakova, V., Krasilnikova, O. et al. 2023. Refinement of animal experiments: Replacing traumatic methods of laboratory animal marking with non-invasive alternatives. Animals 13(22), 3452.

Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than...

Van Loo, P. L. P., Janssens, M. R. E. 2023. Why all healthy laboratory animals should be rehomed, no matter how small. Animals 13(17), 2727.

This paper explores the ethical imperative of rehoming all healthy animals of sentient species after experiments have finished or when they have become otherwise redundant. We take into account disparate perspectives in animal ethics and...

Ferguson, L. T., Rashied, A. A., Liang, Z. et al. 2023. A novel scoring system for humane endpoints in mice with cecal ligation and puncture-induced sepsis. Comparative Medicine 73(6), 446–460.

Animal-based research is essential to the study of sepsis pathophysiology, diagnostics, and therapeutics. However, animal models of sepsis are often associated with high mortality because of the difficulty in predicting imminent death based on premortem...

Chen, D. D., Molk, D. M., Palley, L. S. et al. 2023. Pinna edge biopsy of 7 and 21 day old C57BL/6 mice as a method for identification and genotyping. JAALAS 62(5), 438–448.

Identifying and genotyping mice prior to weaning can be useful for mouse colony management. Mice of an undesired genotype can be identified prior to weaning and removed from further study, resulting in a reduction of...

Runde, B. J., Buckel, J. A., Bacheler, N. M. et al. 2022. Evaluation of six methods for external attachment of electronic tags to fish: Assessment of tag retention, growth and fish welfare. Journal of Fish Biology 101(3), 419-430.

External attachment of electronic tags has been increasingly used in fish studies. Many researchers have used ad hoc attachment methods and provided little or no validation for the assumption that tagging itself does not bias...

Chen, T., Zhou, Z.-Y., Liu, J.-Y. et al. 2022. Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice. Scientific Reports 12(1), 21014.

Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects...

Brough, D. W., Murkin, J. T., Amos, H. E. et al. 2022. Comparing variability in measurement of subcutaneous tumors in mice using 3D thermal imaging and calipers. Comparative Medicine 72(6), 364–375.

Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for measuring subcutaneous tumors in rodents...

Carbone, L. 2021. Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species. Scientific Reports 11(1), 493.

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not...

Rácz, A., Allan, B., Dwyer, T. et al. 2021. Identification of individual zebrafish (Danio rerio): A refined protocol for VIE tagging whilst considering animal welfare and the principles of the 3Rs. Animals 11(3), 616.

In aquatic ecology, studies have commonly employed a tagging technique known as visible implant elastomer (VIE). This method has not been widely adopted by the zebrafish research community and also lacks refinement with regard to...

Kammertoens, T., Jeuthe, S., Baranzke, H. et al. 2021. Breeding and maintenance of immunodeficient mouse lines under SPF conditions—A call for individualized severity analyses and approval procedures. Animals 11(6), 1789.

In the EU, the breeding of genetically modified laboratory animals is, by definition, an animal experiment if the offspring may experience pain, suffering, or harm. In order to determine the actual burden of genetically modified...

Burn, C. C., Mazlan, N. H. B., Chancellor, N. et al. 2021. The pen is milder than the blade: Identification marking mice using ink on the tail appears more humane than ear-punching even with local anaesthetic. Animals 11(6), 1664.

Identification marking mice commonly involves ear-punching with or without anaesthetic, or tail-marking with ink. To identify which is most humane, we marked weanling male BALB/c mice using ear-punching (EP), ear-punching with anaesthetic EMLATM cream (EP+A)...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...

Miller, A. L., Roughan, J. V. 2021. Welfare assessment, end-point refinement and the effects of non-aversive handling in C57BL/6 mice with Lewis lung cancer. Animals 12(1), 23.

Cancer-bearing mice are at risk of developing anxiety, pain, or malaise. These conditions may not only harm welfare but could also undermine data quality and translational validity in studies to develop therapeutic interventions. We aimed...

Young, T., Whiteside, T., Locklear, J. 2020. What is your tattoo ink telling you? Laboratory Animal Science Professional 8(2) (March/April), 62-65.

Tattooing traumatizes the skin, which can result in microbial infections with the severity ranging from minor to life-threating septicemia. Additionally, the metals in colored tattoo ink are known to cause dermal inflammation in some people...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Nwagwu, C. D., Defensor, E., Jiang, M. Y. et al. 2020. Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics. Lab Animal 49(8), 227–232.

Despite several therapeutics showing promise in nonclinical studies, survival from ovarian cancer remains poor. New technologies are urgently needed to optimize the translation of nonclinical studies into clinical successes. While most nonclinical settings utilize subjective...

Aleström, P., D’Angelo, L., Midtlyng, P. J. et al. 2020. Zebrafish: Housing and husbandry recommendations. Laboratory Animals 54(3), 213–224.

This article provides recommendations for the care of laboratory zebrafish (Danio rerio) as part of the further implementation of Annex A to the European Convention on the protection of vertebrate animals used for experimental and...

Wilkinson, M. J. A., Selman, C., McLaughlin, L. et al. 2020. Progressing the care, husbandry and management of ageing mice used in scientific studies. Laboratory Animals 54(3) 225–238.

Driven by the longer lifespans of humans, particularly in Westernised societies, and the need to know more about ‘healthy ageing’, ageing mice are being used increasingly in scientific research. Many departments and institutes involved with...

Kersemans, V., Wallington, S., Allen, P. D. et al. 2020. Manganese-free chow, a refined non-invasive solution to reduce gastrointestinal signal for T1-weighted magnetic resonance imaging of the mouse abdomen. Laboratory Animals 54(4), 353–364.

Commercial mouse chow is designed to provide a complete, nutrient-rich diet, and it can contain upwards of 100 mg/kg manganese, an essential mineral. Manganese acts as a relaxation time-shortening contrast agent for both T1 and T2...